G_i alpha subunit

G_i protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the G_i/o (G_i /G_o ) family or G_i/o/z/t family to include closely related family members. G alpha subunits may be referred to as G_i alpha, G_αi, or G_iα.

Family members

There are four distinct subtypes of alpha subunits in the G_i/o/z/t alpha subunit family that define four families of heterotrimeric G proteins:

• G_i proteins: G_i1α, G_i2α, and G_i3α
• G_o protein: G_oα (in mouse there is alternative splicing to generate G_o1α and G_o2α)
• G_z protein: G_zα
• Transducins (G_t proteins): G_t1α, G_t2α, G_t3α

G_iα proteins

G_i1α

G_i1α is encoded by the gene GNAI1.

G_i2α

G_i2α is encoded by the gene GNAI2.

G_i3α

G_i3α is encoded by the gene GNAI3.

G_oα protein

G_o1α is encoded by the gene GNAO1.

G_zα protein

G_zα is encoded by the gene GNAZ.

Transducin proteins

G_t1α

Transducin/G_t1α is encoded by the gene GNAT1.

G_t2α

Transducin 2/G_t2α is encoded by the gene GNAT2.

G_t3α

Gustducin/G_t3α is encoded by the gene GNAT3.

Function

The general function of G_i/o/z/t is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector.^[1][2] The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as G_iα, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex.^[1][2] When not stimulated by a receptor, Gα is bound to GDP and to Gβγ to form the inactive G protein trimer.^[1][2] When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.^[1][2] GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.

G_i proteins primarily inhibit the

G_z proteins also can link GPCRs to inhibition of adenylyl cyclase, but G_z is distinct from G_i/G_o by being insensitive to inhibition by pertussis toxin.[5]

G_t proteins function in sensory transduction. The Transducins G_t1 and G_t2 serve to transduce signals from G protein-coupled receptors that receive

The following G protein-coupled receptors couple to G_i/o subunits:

• Acetylcholine M₂ & M₄ receptors
• A₃
  receptors
• α_2C
  receptors
• Apelin receptors
• Calcium-sensing receptor
• CB2^[6]
  )
• Chemokine CXCR4 receptor
• D₄
• GABA_B
  receptor
• mGlu₈
  receptors
• Histamine H₃ & H₄ receptors
• MT₃
  receptors
• HCA3
• μ, & nociceptin
  receptors
• FP, & TP
  receptors
• 5-HT₅
  receptors
• FFAR3
• Somatostatin sst1, sst2, sst3, sst4 & sst5 receptors
• Trace amine-associated receptor 8

See also

• Second messenger system
• G protein-coupled receptor
• Heterotrimeric G protein
• Adenylyl cyclase
• Protein kinase A
• Gs alpha subunit
• Gq alpha subunit
• G12/G13 alpha subunits
• Retina
• Taste

References